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1.
Recently, elevated peripheral blood monocyte counts at diagnosis have been shown to be an independent marker associated with poor prognosis in patients with both non-Hodgkin and Hodgkin lymphoma. In this study, we retrospectively analyzed the data from a total of 550 patients with diffuse large B-cell lymphoma and evaluated the relationship between central nervous system relapse and absolute monocyte counts at diagnosis. Twenty-six patients developed central nervous system relapse. The central nervous system relapse-free survival rate was significantly lower in patients with the absolute monocyte counts ≥0.51×109/L (87.8% versus 96.4%; P<0.001). This association was independently significant after adjusting for other significant factors, including systemic relapse as a time-dependent covariate by multivariate analysis (hazard ratio 2.46; 95% confidence intervals 1.05–5.75; P=0.039). These results suggest that the absolute monocyte count at diagnosis is an independent significant risk factor for central nervous system relapse in patients with diffuse large B-cell lymphoma.  相似文献   

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Diffuse large B‐cell lymphoma (DLBCL) is a heterogeneous disease and “double‐hit” DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) or CHOP‐like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event‐free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B‐cell (GCB) type, but not in the non‐GCB type. In DLBCL, high co‐expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk‐adapted therapies.  相似文献   

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Chemotherapy and rituximab (R) is current standard therapy in diffuse large B‐cell lymphoma (DLBCL), but a substantial proportion of patients still fail to reach sustained remission. In vitro studies have indicated that rituximab resistance could be accompanied by dysregulated apoptotic pathways, such as the phosphatidylinositol 3‐kinase (PI3K)/AKT signaling pathway, which can be constitutively activated in DLBCL. In this retrospective, immunohistochemical study on 106 patients treated with R‐CHO(E)P (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab [+etoposide]), we investigated the prognostic role of proteins involved in different apoptotic pathways; phosphorylated AKT (p‐AKT), bcl‐2, MCL1, bcl‐xL, Bax and Bak. High p‐AKT expression (>108 cells/mm2, highest quartile, n = 27) predicted worse progression‐free (PFS) (P = 0·02) and overall (OS) (P = 0·01) survival, independent of International Prognostic Index and sex. Also bcl‐2+ (cut‐off 50%) predicted worse PFS (P = 0·005) and OS (P = 0·05) but after adjustment for clinical factors only the influence on PFS (P = 0·03) remained significant. The prognostic impact of p‐AKT overexpression was independent of bcl‐2 status. MCL1, bcl‐xL, Bax and Bak expression did not add any prognostic information. Our results suggest that high p‐AKT expression predicts worse outcome, possibly indicating that inhibition of the activated PI3K/AKT pathway could be of clinical interest in DLBCL patients. In addition, bcl‐2 status could have prognostic importance also in the era of immunochemotherapy.  相似文献   

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We recently defined event‐free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age‐ and sex‐matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline‐based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c‐statistic = 0.671) in the validation dataset compared to the IPI (c‐statistic = 0.649) or the NCCN‐IPI (c‐statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12–88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps. Am. J. Hematol. 91:179–184, 2016. © 2015 Wiley Periodicals, Inc.  相似文献   

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It is still unclear whether there are clinically exploitable differences in the biology and behaviour of early versus late relapses in diffuse large B‐cell lymphoma (DLBCL). The present study aimed to analyse a large population‐based DLBCL cohort in order to identify (i) the frequency of late relapses (LR), (ii) parameters influencing the risk of LR, and (iii) the impact of introducing rituximab on the occurrence of LR. The data of 7247 DLBCL patients was obtained from the Danish Lymphoma Group Registry. Patients with LR had a lower International Prognostic Index and better performance score than early relapse (ER) patients. The use of radiotherapy lowered only the rate of ER while the use of rituximab yielded a lower occurrence of both ER and LR (P < 0·0001 and P < 0·0001, respectively), possibly suggesting a longer‐lasting biological effect. Additionally, we found a female overrepresentation among LR patients that had received a rituximab‐containing first line treatment. It was found that patients with LR had a significantly better 5‐year overall survival compared to ER patients. In conclusion, LR was more frequently associated with low‐risk features than ER. Furthermore, we found that the use of modern immunochemotherapy regimens in DLBCL lowers the risk of both ER and LR.  相似文献   

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The peripheral blood absolute lymphocyte count (ALC) recovery after autologous stem cell transplantation has been shown to be an independent prognostic factor for survival for different haematologic malignancies. The role of ALC at diagnosis for follicular (grades 1 and 2) lymphomas (FL) on survival is not well described. The primary objective of this study was to assess the role of ALC on overall survival (OS) in FL patients. Of 1104 FL patients, 228 patients were originally diagnosed, followed, and had all treatment at the Mayo Clinic from 1984 and 1999, were evaluated. The median follow-up was 89 months (range: 8.35-248). ALC as a continuous variable was identified as a predictor for OS [Hazard ratio (HR) = 0.74, P < 0.04]. ALC >/= 1.0 x 10(9)/l (n = 164) predicted a longer OS versus ALC < 1.0 x 10(9)/l (n = 64; 175 vs. 73 months respectively, P < 0.0001). When compared with the Follicular Lymphoma International Prognostic Index (FLIPI), ALC was an independent prognostic factor for OS by multivariate analysis (HR = 0.677, P < 0.0001). These data suggest a critical role of FL patients' immune status at diagnosis on survival.  相似文献   

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Cytomegalovirus (CMV) infections post‐haematopoietic stem cell transplantation (HSCT) can be effectively controlled through the adoptive transfer of donor‐derived CMV‐specific T cells (CMV‐T). Current strategies involve a second leukapheresis collection from the original donor to manufacture CMV‐T, which is often not possible in the unrelated donor setting. To overcome these limitations we have investigated the use of a small aliquot of the original granulocyte‐colony stimulating factor (G‐CSF) mobilized HSCT graft to manufacture CMV‐T. We explored the T cell response to CMVpp65 peptide stimulation in G‐CSF mobilized peripheral blood mononuclear cells (PBMC) and subsequently examined isolation of CMV‐T based on the activation markers CD154 and CD25. CD25+ enriched CMV‐T from G‐CSF mobilized PBMC contained a higher proportion of FoxP3 expression than non‐mobilized PBMC and showed superior suppression of T cell proliferation. Expanded CMV‐T enriched through CD154 were CD4+ and CD8+, demonstrated a high specificity for CMV, secreted cytotoxic effector molecules and lysed CMVpp65 peptide‐loaded phytohaemagglutinin‐stimulated blasts. These data provide the first known evidence that CMV‐T can be effectively manufactured from G‐CSF mobilized PBMC and that they share the same characteristics as CMV‐T isolated in an identical manner from conventional non‐mobilized PBMC. This provides a novel strategy for adoptive immunotherapy that abrogates the need for successive donation.  相似文献   

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Richter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8–10 months. We conducted a phase II trial of standard CHOP‐21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) with ofatumumab induction (Cycle 1: 300 mg day 1, 1000 mg day 8, 1000 mg day 15; Cycles 2–6: 1000 mg day 1) (CHOP‐O) followed by 12 months ofatumumab maintenance (1000 mg given 8‐weekly for up to six cycles). Forty‐three patients were recruited of whom 37 were evaluable. Seventy‐three per cent were aged >60 years. Over half of the patients received a fludarabine and cyclophosphamide‐based regimen as prior CLL treatment. The overall response rate was 46% (complete response 27%, partial response 19%) at six cycles. The median progression‐free survival was 6·2 months (95% confidence interval [CI] 4·9–14·0 months) and median OS was 11·4 months (95% CI 6·4–25·6 months). Treatment‐naïve and TP53‐intact patients had improved outcomes. Fifteen episodes of neutropenic fever and 46 non‐neutropenic infections were observed. There were no treatment‐related deaths. Seven patients received platinum‐containing salvage at progression, with only one patient obtaining an adequate response to proceed to allogeneic transplantation. CHOP‐O with ofatumumab maintenance provides minimal benefit beyond CHOP plus rutuximab. Standard immunochemotherapy for RS remains wholly inadequate for unselected RS. Multinational trials incorporating novel agents are urgently needed.  相似文献   

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Prophylactic radiation to the contralateral uninvolved testicle has become a standard practice in the treatment of primary testicular lymphoma. While it is generally felt to be very effective, its failure rate is unknown. We describe a patient with primary testicular diffuse large B‐cell lymphoma, who developed recurrent disease in the contralateral testicle despite receiving prophylactic testicular radiation, central nervous system prophylaxis, and anthracycline‐based chemo‐immunotherapy. Review of the literature shows that the testicular failure rate after prophylactic radiation may be unexpectedly high at 10% or more. We put forward hypotheses on testicular relapse and discuss potential alternative preventive strategies.  相似文献   

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Purpose: Introduction of rituximab has largely improved the prognosis of patients with diffuse large B‐cell lymphoma(DLBCL). Such change in therapeutic outcome necessitates the identification of additional prognostic factors to conventional indexes that have been validated for CHOP without rituximab. Indoleamine 2,3‐dioxygenase (IDO) exerts intense immunomodulatory effects because of enzymatic activities that catalyze the breakdown of the essential amino acid L‐tryptophan. The activity of IDO can be estimated by measuring the serum concentration of L ‐kynurenine. Here, we investigated the role of L ‐kynurenine as a prognostic marker in R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy. Experimental design: Data from 73 consecutive patients treated with eight cycles of R‐CHOP or R‐THP (tetrahydropyranyl adriamycin)‐COP between December 2002 and March 2007 were analyzed. L ‐kynurenine concentrations in serum samples obtained at admission were measured by high‐performance liquid chromatography. Results: The median serum L ‐kynurenine level was 1.575 μm (range 0.537–9.588). The complete response (CR) rates of patients with L ‐kynurenine <1.5 and ≥1.5 μm were 83% and 61%, respectively (P < 0.05). The three‐yr overall survival (OS) rates for patients with L ‐kynurenine <1.5 and ≥1.5 μm were 89% and 58%, respectively (P < 0.005). In addition, higher age, poor performance status, elevated serum lactate dehydrogenase, and unfavorable as well as revised International Prognosis Index were significantly worse factors for CR rate and OS. Multivariate analyses revealed only L ‐kynurenine as an independent prognostic factor for OS. Conclusions: Serum L ‐kynurenine might be a novel prognostic factor to determine the treatment outcome of DLBCL with the R‐CHOP regimen.  相似文献   

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‘Wrong blood in tube’ (WBIT) errors, where the blood in the tube is not that of the patient identified on the label, may lead to catastrophic outcomes, such as death from ABO‐incompatible red cell transfusion. Transfusion is a multistep, multidisciplinary process in which the human error rate has remained unchanged despite multiple interventions (education, training, competency testing and guidelines). The most effective interventions are probably the introduction of end‐to‐end electronic systems and a group‐check sample for patients about to receive their first transfusion, but neither of these eradicates all errors. Further longer term studies are required with assessment before and after introduction of the intervention. Although most focus has been on WBIT in relation to blood transfusion, all pathology samples should be identified and linked to the correct patient with the same degree of care. Human factors education and training could help to increase awareness of human vulnerability to error, particularly in the medical setting where there are many risk factors.  相似文献   

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Background: Malignant lymphoma with central nervous system (CNS) involvement has an extremely poor prognosis. We retrospectively studied the risk factors for CNS involvement in patients with diffuse large B‐cell lymphoma (DLBCL) treated by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab (R) ‐CHOP chemotherapy. Patients and methods: We studied 375 consecutive patients who were newly diagnosed with DLBCL between 1996 and 2006. Patients with primary CNS involvement and patients who received CNS prophylaxis were excluded. All the patients received CHOP (n = 172) or R‐CHOP (n = 203) chemotherapy. The following variables were assessed for their potential to predict CNS involvement: gender, age, serum lactate dehydrogenase (LDH) level, performance status, clinical stage, number of extranodal involvements, International Prognostic Index (IPI), bone marrow involvement, presence of a bulky mass, presence of B symptom, and treatment. Results: CNS involvement was observed in 13 cases (3.5%). In univariate analysis, LDH more than normal range, LDH more than twice as normal range, high IPI, bone marrow involvement, and systemic relapse were the predictors for CNS involvement. In multivariate analysis, no risk factors were detected for CNS involvement. The use of rituximab did not have an impact on CNS involvement. Conclusions: The incidence of CNS involvement dose not decrease in rituximab‐era.  相似文献   

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International prognostic index (IPI) has remained the primary prognostic tool in diffuse large B cell lymphoma (DLBCL) for more than 20 years. Even though the disease is more common in older population, the impact of comorbidities, dose reductions, and treatment‐related adverse events (TAEs) on the outcome in elderly DLBCL patients has not been well established. We studied 413 consecutive patients aged ≥ 60 years who were treated at the Cleveland Clinic. The median age at diagnosis was 69 years, 58% of patients had high IPI score, and 85% had low Charlson comorbidity index (CCI). Forty percent of patients required dose reductions during treatment, 78% achieved CR, and 70% experienced at least one grade II‐IV TAE. High IPI score, high CCI, reduced dose chemotherapy, TAE, and hospitalization were significant predictors of death and relapse. In multivariable analysis, high IPI and CCI were independent predictors of overall and progression free survival. A simple model combining IPI and CCI could reliably distinguish three prognostically separate risk groups. Our results suggest that incorporation of CCI in current prognostic models can improve prognostication of older DLBCL patients and CCI might be a valuable tool in evaluating the eligibility of older patients for clinical trial enrollment.  相似文献   

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